Objective: To analyze the health literacy possession rate and its trend among residents in Lishui City, Zhejiang Province from 2016 to 2024, so as to provide the evidence for improving health promotion strategies and intervention measures. Methods: Multi-stage stratified random sampling combined with probability proportionate to size sampling method was adopted to select permanent residents aged 15-69 years in Lishui City as survey subjects. Demographic information and health literacy possession status were collected through questionnaire survey. The health literacy possession rate was calculated. The data from 2016 to 2019 and from 2020 to 2024 were standardized using the population data of Lishui City from the Sixth National Population Census in 2010 and the Seventh National Population Census in 2020, respectively. The trend of health literacy possession rate from 2016 to 2024 was analyzed. Results: A total of 42 691 people were surveyed, including 20 509 males (48.04%) and 22 182 females (51.96%), with an average age of (51.63±12.13) years. From 2016 to 2024, the health literacy possession rates were 20.40%, 25.83%, 26.96%, 28.82%, 32.30%, 34.02%, 37.53%, 39.21% and 43.17%, respectively, showing an upward trend (P<0.05). Among the three aspects, the possession rates of basic knowledge and concepts, healthy lifestyle and behaviors, and basic skills all showed upward trends (all P<0.05), with basic knowledge and concepts showing the largest increase and basic skills showing the smallest increase. Among the six health issues, the possession rates of scientific health view, chronic disease prevention and control, safety and first aid, basic medical care, and health information showed upward trends, while the infectious disease prevention and control literacy possession rate showed a downward trend (all P<0.05). The possession rates in the 65-69 age group, illiterate/semi-literate residents, and farmers showed upward trends (all P<0.05), but with small increases and remaining at low levels. Conclusions From 2016 to 2024, the health literacy possession rate of residents in Lishui City showed an overall upward trend, but the increase in basic skills literacy possession rate was relatively slow, and the infectious disease prevention and control literacy possession rate showed a downward trend. It is necessary to strengthen health education for weak links and knowledge among elderly people, residents with low educational level, and farmers to improve health literacy level.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl₄) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.

Objective To investigate the predictive value of the combined tumor burden score (TBS) and platelet-albumin-bilirubin (PALBI) score model for postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma (HCC). Methods The general information of 158 recipients diagnosed with HCC and underwent liver transplantation at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from 2008 to 2021 was collected. Lasso regression analysis combined with multivariate Cox regression analysis were used to identify independent risk factors for postoperative tumor recurrence after liver transplantation with HCC. A nomogram prediction model was constructed based on variables selected by Lasso regression analysis, and the predictive performance of the model was verified by calibration curve and clinical decision curve. The optimal cut-off values for postoperative tumor recurrence in liver transplant recipients with HCC were determined by receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis was used to compare survival differences among different groups. Results Among the 158 liver transplant recipients with HCC, 82 experienced tumor recurrence, with a recurrence rate of 51.9% and a median tumor-free survival time of 10 (4, 25) months. Results of Lasso regression analysis and multivariate Cox regression analysis showed that alpha-fetoprotein (AFP) ≥400 ng/mL, TBS and PALBI score were all independent risk factors for postoperative tumor recurrence in liver transplant recipients with HCC (all P<0.05). The combined high TBS-high PALBI score showed the highest predictive value (hazard ratio 6.909, 95% confidence interval 3.067-15.563, P<0.001). A nomogram prediction model was constructed based on six variables selected by Lasso regression analysis. Calibration curve showed good consistency between the model's predicted results and the ideal curve. Decision curve analysis indicated that the nomogram prediction model provided the highest clinical benefit for predicting 1-year tumor-free survival after liver transplantation with HCC. Time-dependent ROC curves at 1, 3 and 5 years after surgery showed that TBS-PALBI model had good predictive performance, with no significant difference in area under the curve (AUC) compared with TBS-PALBI-AFP model. The optimal cut-off values for predicting postoperative tumor recurrence were determined by ROC curve, with a PALBI score cut-off of −2.334 and a TBS cut-off of 5.305. Recipients were divided into a low TBS-low PALBI score group (n=47) and a low/high TBS-low/high PALBI score group (at least one score was high) (n=111). Kaplan-Meier survival analysis showed that the low TBS-low PALBI score group had a higher tumor-free survival rate than the low/high TBS-low/high PALBI score group, with a significant difference (P<0.05). Conclusions TBS-PALBI model provides a novel, simple and effective tool for assessing the prognosis of liver transplant recipients with HCC. The nomogram model constructed based on this has significant advantages in predictive performance and may serve as a reference for guiding individualized treatment plans and improving clinical outcomes.

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

OBJECTIVE: To evaluate the effects of Chinese patent medicine Huatuo Zaizao Pill (HTZZ) on neurological function and limb motor in ischemic stroke (IS) patients during convalescence. METHODS: This is a prospective, open-labelled, randomized controlled trial. Patients with IS were recruited from the Neurology Department of Xiyuan Hospital of China Academy of Chinese Medical Sciences from May 2021 to June 2023. Eligible participants were randomly assigned to the HTZZ (40 cases) or control group (40 cases) at a ratio of 1:1. The HTZZ group was treated with oral HTZZ (8 g, thrice daily) combined with conventional treatment, while the control group received only conventional treatment. The treatment duration was 12 weeks. The primary outcome was the change in Modified Ashworth Scale (MAS) score from baseline to week 6 and 12. Secondary outcomes included changes in scores of National Institute of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment (FM), and Barthel Index (BI) from baseline to week 6 and 12, as well as lipid indices after 12 weeks. All adverse events (AEs) were recorded and liver and kidney indices were evaluated. RESULTS: A total of 72 patients completed the study (38 in the HTZZ group and 34 in the control group). Compared with the control group, the HTZZ group demonstrated significant improvements in MAS, NIHSS, FM, and BI scores following 6 and 12 weeks of treatment in both intent-to-treat and per-protocol analyses (all P<0.05). No significant differences were noted between groups in lipid indices, AEs, and liver and kidney dysfunction after 12 weeks (P>0.05). CONCLUSIONS HTZZ alleviated spasticity and enhanced neurological function and prognosis of IS patients during convalescence. However, further evaluation of HTZZ's effect on IS outcomes is warranted in clinical trials with larger sample sizes and extended observation periods. (Trial registration No. NCT04910256).
Humans ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Ischemic Stroke/physiopathology* ; Middle Aged ; Aged ; Recovery of Function/drug effects* ; Convalescence ; Extremities/physiopathology* ; Treatment Outcome ; Prospective Studies

Objective:To evaluate the clinical features and risk factors of anastomotic leakage (AL) in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (nCRT) followed by laparoscopic radical resection and proctocol ostomy.Method:Clinicla data of LARC patients receiving neoadjuvant chemoradiotherapy followed by laparoscopic radical resection and proctocol ostomy admitted to Peking Union Medical College Hospital between Jan 2019 and Oct 2023 was enrolled. According to the occurrence of AL, patients were divided into AL group and non-AL group.Results:After propersity matching score(PSM), there were 40 patients (33.4%) and 80 patients (66.6%) in the AL and non-AL group, respectively. The first-onset symptoms of AL were abnormal character and color of the drainage (23 cases, 57.5%) and fever (14 cases, 35.0%). About 82.5% of the AL were graded as B,and all 36 patients (90.0%) were managed consveratively by fully drainage anti-infection therapy. Logistic regression analysis indicated that tumor circumferential range more than 1/2 cycle ( OR=5.95, 95% CI:2.12-1.67, P=0.004), male ( OR=4.28, 95% CI:1.22-15.00, P=0.023) and high-ligation of Inferior mesenteric artery ( OR=8.08, 95% CI:1.86-37.78, P=0.006) were independent risk factors of AL. Conclusions:In this series, grade-B AL ranks the top of the incidence, and all were cured by conservative therapy. Special attention should be paid to those patients with the characteristics of male, tumor circumferential range more than 1/2 cycle, and high-ligation of inferior mesenteric artery.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.